DESCRIPTION: (Applicant's Abstract) High rates of relapse to drug use characterize the behavior of experienced heroin and cocaine users. In the proposed research, we will use an animal model to study the neurochemical basis of relapse to drug taking induced by stress. Stress has long been thought to play an important role in relapse in humans, and we have now shown in a series of experiments that it is a powerful inducer of relapse to drug taking in rats after prolonged drug-free periods. We have found that the constellation of neurochemical events involved in relapse induced by stress is distinct from that induced by drugs and that corticotropin-releasing factor and noradrenaline contribute significantly to stress-induced relapse. On the basis of these findings, we now propose to further characterize neurochemical events involved in relapse to cocaine and heroin induced by stressors. Using a reinstatement model in which events that induce relapse to drug seeking can be studied after prolonged drug-free periods in experienced drug users, we aim to identify further the neurotransmitters and brain sites involved in the effect of stress on relapse. Using microdialysis, we will assess the neuronal adaptations that may account for susceptibility to stress-induced relapse that is present after chronic exposure to drugs. Further characterization of the relapse processes in our preclinical model may lead to a better understanding of relapse to drug taking and to the development of medications to prevent relapse in humans.